The object of this proposal is to test the transmethylation hypothesis of schizophrenia by measuring n vivo the kinetics of 11C-methyl-methionine in the brainof schizophrenics and controls. This will be accomplished by the combined application of seven advanced techniques: 1) cyclotron production of carbon-11 and synthesis of 1C-methyl-L-methionine; 2) X-ray computed tomography for determination of precise anatomical references; 3) dynamic emission computed tomography of the 11C-methyl kinetics in the plane of the limbic system; 4) brain blood volume determination and intravascular flow by 82RB PET scanning; 5) 11CO2 kinetics by ionization chamber respirometry; 6) HPLC analysis of plasma for 11C-labelled metabolites; 7)computer analysis of data and use of compartment model systems to describe normal and abnormal methyl metabolism. Patient source and clinical evaluation is provided by the NIH Mental Health Clinical Research Center at Palo Alto, and our data will be correlated with their other studies including CSF metabolites. The unique combination of high technology machines developed at this laboratory provides an unusual opportunity for a concerted investigateion of the biochemistry of patients with mental disorders. It is anticipated that the data so obtained will provide better understanding of methyl carbon metabolism in a schizophrenia, and eventually lead to design of more successful methods of treatment.